Project Summary: Gastroesophageal reflux disease (GERD), a common chronic disorder in the veteran population, is associated with drug costs exceeding $ 10 billion/year. Only 30-40% of patients with reflux symptoms have erosive esophagitis. The vast majority suffers from NERD;a condition in which standard endoscopy fails to identify any mucosal breaks and is unable to confirm the diagnosis. Unfortunately, a gold standard for the diagnosis of NERD does not exist. 24-hour esophageal pH monitoring and histologic esophageal mucosal changes in NERD patients have limited accuracy to be routinely used in clinical practice. Narrow band imaging (NBI) utilizes spectral narrow band filters (incorporated into standard endoscopes) and enables imaging of features such as intrapapillary capillary loops (IPCLs);features not identified during standard endoscopy. Preliminary results have shown that NBI endoscopy may represent a significant improvement over standard endoscopy for the diagnosis of NERD. Our hypothesis is that NBI identifies changes in the distal esophagus that are specific for diagnosing patients with NERD. Specific Aim #1: To compare NBI features in the distal esophagus in patients with NERD (cases) and controls. Specific Aim #2: To determine whether the NBI features in NERD patients resolve after PPI therapy. Specific Aim #3: To correlate NBI findings with esophageal histology. Specific Aim #4: To assess the intra- and interobserver agreement for recognition of the proposed criteria for diagnosing NERD. Cases will be defined as patients with reflux symptoms (assessed by two validated questionnaires) with absent macroscopic erosions and abnormal esophageal pH results (NERD group). Control subjects will include patients with no reflux symptoms, absent macroscopic erosions and a normal esophageal pH result. To identify NBI findings as predictors of response, response to therapy in cases randomized to the PPI arm will be assessed using a validated GERD questionnaire and correlated with IPCL number and presence of microerosion. In addition, NBI findings in patients with reflux symptoms, no macroscopic erosions and normal esophageal pH result will also be compared with controls. Two biopsies will be obtained from the distal esophagus along with digital images and video- recordings. Statistical analysis will be done as follows: Aim 1 - chi-square and t-test;with logistic regression and calculation of odds ratios, Aim 2- McNemar's test and kappa statistic, Aim 3- Spearman's correlation coefficient and Aim 4- intraclass correlation coefficient. Potential impact on Veterans Health Care: GERD is common among veterans and by obviating the need for additional investigations and reducing unnecessary drug costs, NBI endoscopy could have a considerable positive impact on veterans with NERD. PUBLIC HEALTH RELEVANCE: Project Narrative: Acid reflux disease is common among veterans and associated with drug costs exceeding $ 10 billion/year. By obviating the need for additional investigations and reducing unnecessary drug costs, Narrow Band Imaging (NBI) endoscopy could have a considerable positive impact on veterans with acid reflux.